In patients with mitral stenosis, valve orifice calculations using pulmonary capillary wedge pressure as a substitute for left atrial pressure may overestimate the severity of disease. Previous studies have shown that mitral valve area determined from transseptal left atrial pressure measurements exceeds that area derived from pulmonary wedge pressure measurements. This is probably due to pulmonary venoconstriction, which is reversed by nitroglycerin. Nitroglycerin, 0.4 mg, was administered sublingually to 20 patients with mitral valve disease during preoperative cardiac catheterization using the pulmonary capillary wedge pressure as the proximal hydraulic variable. At the time of a peak hypotensive effect, 3 to 5 minutes after nitroglycerin administration, the mean pulmonary capillary wedge pressure decreased from 23 +/- 2 (mean +/- SEM) to 19 +/- 2 mm Hg (p less than 0.005). The mean diastolic transmitral pressure gradient (12.6 +/- 1.2 mm Hg before and 11.5 +/- 1.0 mm Hg after nitroglycerin; p = NS) and cardiac output (4.0 +/- 0.3 to 4.1 +/- 0.3 liters/min; p = NS) did not change significantly. Nevertheless, the hemodynamic mitral orifice area, calculated using the Gorlin formula, increased from 0.8 +/- 0.1 to 1.1 +/- 0.2 cm2 (p less than 0.05). In 12 patients with isolated mitral stenosis, without regurgitation, the mitral valve orifice area after nitroglycerin was 0.4 +/- 0.2 cm2 larger than it was before drug administration (p less than 0.05). Administration of nitroglycerin during evaluation of mitral stenosis eliminates pulmonary venoconstriction, which raises the pulmonary capillary wedge pressure above the left atrial pressure in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)